Causal effects of COVID-19 on the risk of thrombosis: A Two-Sample Mendel Randomization Study.

BACKGROUND: COVID-19 and thrombosis are linked, but the biomolecular mechanism is unclear. We aimed to investigate the causal relationship between COVID-19 and thrombotic biomarkers.

METHODS: We used Two-sample Mendelian Randomization (MR) to assess the effect of COVID-19 on 20 thrombotic biomarkers. We estimated causality using Inverse variance weighting with multiplicative random effect, and performed sensitivity analysis using weighted median, MR Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. We used R language for the analysis.

RESULTS: All COVID-19 classes showed lower levels of tissue factor pathway inhibitor (TFPI) and interleukin-1 receptor type 1 (IL-1R1). COVID-19 significantly reduced TFPI (OR=0.639, 95%CI: 0.435-0.938) and IL-1R1 (OR=0.603, 95%CI=0.417-0.872), nearly doubling the odds. We also found that COVID-19 lowered multiple coagulation factor deficiency protein 2 (MCFD2) and increased C-C motif chemokine 3 (CCL3). Hospitalised COVID-19 cases had less plasminogen activator, tissue type (tPA) and P-selectin glycoprotein ligand 1 (PSGL-1), while severe cases had lower mean platelet volume (MPV) and platelet count. These changes in TFPI, tPA, IL-1R1, MPV and platelet count suggested a higher risk of thrombosis. Decreased PSGL-1 indicated a lower risk of thrombosis.

CONCLUSIONS: This study demonstrated that COVID-19 causally influences thrombosis at the biomolecular level, mainly by reducing TFPI and IL-1R1. Three other biomarkers also implied that COVID-19 increases thrombosis risk. We confirmed the reduction of platelet count and MPV, providing clues to the pathogenesis of COVID-19 and thrombosis. Our findings may have implications for the prevention and treatment of thrombotic complications in COVID-19 patients.